Результаты поиска

Phenylketonuria as a protein misfolding disease: The mutation pG46S in phenylalanine hydroxylase promotes self-association and fibril formation.

The missense mutation pG46S in the regulatory (R) domain of human phenylalanine hydroxylase (hPAH), associated with a severe form of phenylketonuria, generates a misfolded protein which is rapidly degraded on expression in HEK293 cells. When overexpressed as a MBP-G46S fusion protein, soluble and fully active tetrameric/dimeric forms are assembled and recovered in a metastable conformational state. When MBP is cleaved off, G46S undergoes a conformational change and self-associates with a lag phase and an autocatalytic growth phase (tetramers≫dimers), as determined by light scattering. The self

Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic.

Sera from patients with chronic Chagas heart disease recognize the carboxyl-terminal regions of the Trypanosoma cruzi ribosomal P proteins defined by B cell epitopes P013 (EDDDDDFGMGALF) and R13 (EEEDDDMGFGLFD) corresponding to the T. cruzi ribosomal P0 (TcP0) and P2beta (TcP2beta) proteins, respectively. It has been hypothesized that both epitopes may induce antibodies that cross-react and stimulate the beta1-adrenoreceptor. However, no proof as to their pathogenicity has been obtained. We investigated the consequences of immunizing mice with either TcP0 or TcP2beta proteins. Of 24 immunized

Identification of small-molecule inhibitors of Yersinia pestis Type III secretion system YscN ATPase.

Yersinia pestis is a gram negative zoonotic pathogen responsible for causing bubonic and pneumonic plague in humans. The pathogen uses a type III secretion system (T3SS) to deliver virulence factors directly from bacterium into host mammalian cells. The system contains a single ATPase, YscN, necessary for delivery of virulence factors. In this work, we show that deletion of the catalytic domain of the yscN gene in Y. pestis CO92 attenuated the strain over three million-fold in the Swiss-Webster mouse model of bubonic plague. The result validates the YscN protein as a therapeutic target for pla

When Iron Bites Back: Severe Thrombocytopenia After Intravenous Iron Sucrose Therapy (Venofer).

Iron deficiency anemia (IDA) commonly presents with normal or elevated platelet counts, while thrombocytopenia is rare. Intravenous iron sucrose (Venofer) is widely used and generally well tolerated. We report the case of a 71-year-old female with chronic IDA who developed severe thrombocytopenia following iron sucrose therapy. Baseline hemoglobin was 6.3 g/dL with a platelet count of 229 × 10³/µL. After two doses of intravenous iron, hemoglobin improved to 9.3 g/dL, but platelets rapidly declined to 11 × 10³/µL. Extensive workup excluded thrombotic microangiopathy, autoimmune disease, infecti

Совпадение в полном тексте источника
… Records of 308 patients demonstrated a dose-dependent reduction in platelet counts (mean 425 G/L to 320 G/L; p < 0.001), independent of iron formulation (iron sulfate, iron sucrose, or ferric carboxy maltose). … The ThromboVIT trial, a single-blinded, placebo-controlled, randomized study, evaluated the effect of ferric carboxy maltose (FCM) in IBD patients with secondary thrombocytosis (platelets > 450 G/L) [ 10 ]. A total of 26 patients were enrolled, with 15 included in the per-protocol analysis. …

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies.

In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new know

Совпадение в полном тексте источника
… | - | - | - Hyperprolinemia | - | - | - | - | x L-proline | - | - Hereditary fructose intolerance | - | - | - | x Sorbitol | - | - | - Corn allergy | - | - | - | x Maltose | - | - | - Seniors | x | x | x | x Glucose | - | - | - | | | | | | | Newborn/children | x | x | x | - | - | x | - Chart … | - | - | - | - OCTAGAM ® 5% solution | Octapharma | Maltose | ≤0.015mmol/mL | 310-380mOsmol/Kg | 5.1-6.0 | <0.2mg/mL OCTAGAM ® 10% solution | Octapharma | Maltose | ≤0.03mmol/mL | ≥240mOsmol/Kg | 4.5-5.0 | <0.4mg/mL Privigen | CSL Behring | Does not contain | Does not contain | 320mOsmol/kg | 4.8 | …

[Study on the situation of plague in Junggar Basin of China].

OBJECTIVE: To understand the distribution, fauna, population structure of host animals and their parasitic fleas as well as popular dynamic … d. The biochemical properties of these Y. pestis which isolated from Junggar Basin were positive of Maltose, Ejiao sugar and Glycerol, and negative of Rhamnose and Nitrogen, which were all strongly poisonous to mouse. CONCLUSION: The natural plague foci in Junggar Basin spread all over the whole Junggar Basin. There were animal plague cases found in 12 c …

Mucin1 as a potential molecule for cancer immunotherapy and targeted therapy.

Mucin1 is a highly glycosylated type 1 transmembrane mucin that ranks second among 75 tumor-related antigens published by the National Cancer Institute, and has been identified as a possible therapeutic target over the past 30 years. MUC1 plays an important role in malignant transformation and disease evolution, including cell proliferation, survival, self-renewal, and metastatic invasion. MUC1 has been shown to interact with diverse effectors such as β-catenin, receptor tyrosine kinases, and cellular-abelsongene, which are of importance in the pathogenesis of various malignant tumors. Targeti

Совпадение в полном тексте источника
… These vaccines either conjugate or mix with a variety of immune agonists, including keyhole limpet hemocyanin (KLH) 73 , mannan 74 , 75 , bacillus Calmette-Guerin (BCG) 76 , maltose binding protein (MBP) 77 , 78 , Quillaja saponaria extract (QS-21), or SB-AS2 79 , in order to improve the immunogenicity … MUC1 and maltose-binding protein recombinant fusion protein combined with Bacillus Calmette-Guerin induces MUC1-specific and nonspecific anti-tumor immunity in mice. Mol Med Rep. 2014;10(2):1056–1064. doi: 10.3892/mmr.2014.2306. 78. Hu B, Wang J, Guo Y, Chen T, Ni W, Yuan H, Zhang N, Xie F, Tai G. …

Extending the CD4(+) T-cell epitope specificity of the Th1 immune response to an antigen using a Salmonella enterica serovar typhimurium delivery vehicle.

We analyzed the CD4 T-cell immunodominance of the response to a model antigen (Ag), MalE, when delivered by an attenuated strain of Salmonella enterica serovar Typhimurium (SL3261*pMalE). Compared to purified MalE Ag administered with adjuvant, the mapping of the peptide-specific proliferative responses showed qualitative differences when we used the Salmonella vehicle. We observed the disappearance of one out of eight MalE peptides' T-cell reactivity upon SL3261*pMalE immunization, but this phenomenon was probably due to a low level of T-cell priming, since it could be overcome by further imm

Связь между потреблением углеводов в рационе питания и множественным риском склероза: широкомасштабное когортное исследование.

ВВЕДЕНИЕ: Множественный склероз (MS) представляет собой хроническое аутоиммунное расстройство, характеризующееся нейроинфламмацией и обезвоживанием. Несмотря на то, что диета может влиять на риск, связанный с НР, доказательства, касающиеся потребления углеводов, остаются неясными. Мы изучили эту ассоциацию в будущей группе 210,483 - участники из Биобанка Соединенного Королевства. Оценка углеводов в рационе питания производилась с использованием повторных методов 24-hour напоминает. Диагностика случаев заболевания синдромом MS основана на больничных больничных данных, кодированных в соответстви

Совпадение в полном тексте источника
… 18.57 (6.18) | 22.56 (8.45) Fructose (g/d), median (IQR) | 17.93 (12.78) | 24.55 (13.90) | 29.23 (15.66) | 36.45 (21.27) Glucose (g/d), median (IQR) | 16.56 (10.58) | 22.82 (11.36) | 27.44 (12.89) | 34.72 (18.02) Lactose (g/d), median (IQR) | 9.98 (8.07) | 12.59 (8.40) | 14.27 (8.89) | 16.51 (10.50) Maltose … | 1.24 (1.13–1.37) | <0.001 | <0.001 | 1.25 (1.12–1.39) | <0.001 | 0.001 Glucose | 1.15 (1.04–1.26) | 0.007 | 0.016 | 1.21 (1.09–1.33) | <0.001 | 0.001 | 1.20 (1.08–1.34) | 0.001 | 0.003 Lactose | 0.98 (0.88–1.09) | 0.718 | 0.783 | 0.98 (0.88–1.10) | 0.750 | 0.750 | 0.99 (0.89–1.11) | 0.894 | 0.894 Maltose …

Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients.

BackgroundMCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902).MethodsBinding of ABBV-467 to human MCL-1 was assessed in multiple cell lines. The ability of ABBV-467 to induce tumor growth inhibition was investigated in xen

Совпадение в полном тексте источника
… X-ray crystallography Protein The MCL-1 compound structures utilized a maltose-binding protein Mcl-1 fusion construct as follows: 6His-(TEV)-G-[MBP (27-392)]-GS-[Mcl-1 (173-321) K194A, K197A, R201A]. The protein was expressed in E. coli BL21 (DE3) cells. … Just prior to crystallization, maltose was added to give 2 mM and glycerol was also added to give 5% (v/v). Crystallization and data collection Crystals were grown and diffraction data were collected for each compound as follows. …

The Role of Purported Mucoprotectants in Dealing with Irritable Bowel Syndrome, Functional Diarrhea, and Other Chronic Diarrheal Disorders in Adults.

Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing

Совпадение в полном тексте источника
… (from 12.7 ± 3.8 to 7.7 ± 2.1 vs. 11.8 ± 3.3 to 9.05 ± 2.2, P < 0.05) Chang F-Y, 2007 [ 154 ] Taiwan 3 g diosmectite/8 h vs. placebo/8 h (0.8 g hydrated glucose, 1.1 g corn starch, 0.008 g saccharin sodium, 0.192 g talcum power, 1.11 g maltose dextrins, 0.006 g caramel coloring [E150], and 0.004 g vanilla … (from 12.7 ± 3.8 to 7.7 ± 2.1 vs. 11.8 ± 3.3 to 9.05 ± 2.2, P < 0.05) Chang F-Y, 2007 [ 154 ] | Taiwan | 3 g diosmectite/8 h vs. placebo/8 h (0.8 g hydrated glucose, 1.1 g corn starch, 0.008 g saccharin sodium, 0.192 g talcum power, 1.11 g maltose dextrins, 0.006 g caramel coloring [E150], and 0.004 …

Микробиомы воспаления имеют функциональную патогенность, предсказанную реактивным белком C.

Мы изучаем специфические по болезням и перекрестные заболевания человеческого кишечного микробиома путем колонизации мышей, свободных от микробов, подверженных риску возбудителя артрита, колита или нейроинфламмы, с более чем 100 фекальными микробиомами человека от лиц с ревматоидным артритом, анкилосирующим спондилитом, множественным склерозом, язвительным колитом, болезнью Крона или раком цвета. Мы находим типичные воспалительные фенотипы, приводимые в действие микробиомами у лиц с кишечным воспалением или подстрекательским артритом, а также различные функции, характерные для микробиомов, у п

Совпадение в полном тексте источника
… Human fecal samples were frozen and stored at −20°C before homogenization under strict anaerobic conditions in pre-reduced LYBHI media (37 g/L BD Brain Heart Infusion, 5 g/L yeast extract, 1 g/L D-xylose, D-fructose, D-galactose, cellubiose, maltose and sucrose, 0.5 g/L N-acetylglucosamine and L-arabinose …

Кристальная структура и каталитический механизм дрименоловой синтазы, необычная двухфункциональная терпеновая киклаза-фосфатаза.

Дрименол синтаза из Aquimarina pongiae (ASDMS) — очень необычная химера, интегрирующая two - отдельные, последовательные операции по переработке изопреноидов в рамках единой полипептидной цепи. ASDMS катализирует циклизацию фарнесилового дифосфата (FPP) класса II для образования дрименилового дифосфата, который затем подвергается гидролизу энзим-катализу для получения дрименинола, биоактивного сескитерпенового спирта с антифунгальными и антираковыми свойствами. Здесь мы сообщаем рентгеновские кристаллы ASDMS и его комплекс с сескитерпен тиол. Структура ASDMS имеет дидомаиновую архитектуру, сос

Совпадение в полном тексте источника
… Anticipating that these residues might be disordered in the full-length protein, a pET-His6-MBP-TEV-AsDMS plasmid lacking these residues was designed (His6 = hexahistidine purification tag, MBP = maltose binding protein, TEV = tobacco etch virus protease), codon-optimized for expression in Escherichia …

Несапонин из Панакс Гинсенг поддерживает целостность мозгового барьера, подавляя NF-ИБ и p38 MAP cinase сигнализирующих путей для предотвращения развития экспериментального аутоиммунного энцефаломиэлита.

НЕСАпонинская (NS) фракция является важным активным компонентом Панакс Гинсенга, имеющей многофункциональную фармакологическую деятельность, включая нейрозащиту, иммунную регламентацию, противовоспалительные и антиоксидантные эффекты. Однако воздействие НС на множественный склероз (МС) - хроническое и аутоиммунное демиелионирующее расстройство - пока еще не доказано. Цель настоящего исследования состояла в том, чтобы продемонстрировать фармакологические действия НСУ по дисфункциям движения и соответствующие механизмы действий с использованием экспериментальной аутоиммунной энцефаломиелитной мо

Совпадение в полном тексте источника
… NS fraction contained polysaccharides [galacturonic acid (25.23 mg/g) + galactose (18.90 mg/g) + arabinose (13.80 mg/g) = 56.20 mg/g], arginyl-fructosyl-glucose (17.94 mg/g), and free sugars [glucose (1.22 %) + fructose (1.83 %) + sucrose (5.63 %) + maltose (6.05 %) = 14.73 %]. …

Interferon-Based Biopharmaceuticals: Overview on the Production, Purification, and Formulation.

The advent of biopharmaceuticals in modern medicine brought enormous benefits to the treatment of numerous human diseases and improved the well-being of many people worldwide. First introduced in the market in the early 1980s, the number of approved biopharmaceutical products has been steadily increasing, with therapeutic proteins, antibodies, and their derivatives accounting for most of the generated revenues. The success of pharmaceutical biotechnology is closely linked with remarkable developments in DNA recombinant technology, which has enabled the production of proteins with high specific

Совпадение в полном тексте источника
… Seven fusion tags—thioredoxin (Trx), hexahistidine (6x His), maltose-binding protein (MBP), N-utilization substance protein A (NusA), protein disulfide isomerase (PDI), GST, and b’a’ domain of PDI (PDIb’a’)—were evaluated for soluble overexpression of codon-optimized IFNα-2b at two different expression … Recombinant proteins produced with attached amino acid sequences as fusion partners-“ tags ”-(GST, maltose-binding domain, hexahistidine–6xHis, among others) exhibit high specificity and affinity to chromatographic resins [ 39 , 51 , 56 ]. …

Перевозка и сдерживание движения sphingosine-1-phosphate Экспортеры SPNS2.

Sphingosine-1-phosphate (S1P) — сигнал лизолипида, имеющий решающее значение для развития сердца, иммунитета и слуха. Соответственно, мутации в переносчике S1P SPNS2 связаны с уменьшением числа белых клеток и нарушениями слуха. СПНС2 также экспортирует S1P-mimicking FTY720-P (Финголимод) и, таким образом, является центральным элементом фармакокинетики этого препарата при лечении множественного склероза. Здесь мы используем комбинацию крио-электронной микроскопии, иммунофлюоресценции, связывания in vitro и в vivo S1P-оценки экспорта, а также молекулярное моделирование динамики для исследования

Совпадение в полном тексте источника
… generation and subcellular localization To enable nanobody generation, biophysical, and structural studies of SPNS2, we first over-expressed the protein in HEK293 cells using the BacMam system and purified the protein to homogeneity as a monomeric species in n-dodecyl-β-D-maltopyranoside (DDM) or lauryl maltose …

IgG replacement in multiple myeloma.

T cell engagers (TCE) such as chimeric antigen receptor (CAR) T cell therapy and bispecific antibodies (BiAbs) for the treatment of multiple myeloma (MM) have significantly improved clinical outcomes, but have also raised awareness for ensuing post-treatment secondary immunodeficiency and hypogammaglobulinemia (HG). As patients with MM live longer, recurrent infections become a significant component of therapy-associated morbidity and mortality. Treatment of HG with immunoglobulin G replacement therapy (IgG-RT) has been a mainstay of the primary immunodeficiency (PI) world, and extrapolation t

Совпадение в полном тексте источника
… However, renal injury has also been reported with maltose and glucose containing products. …

The Effects of Artificial Sweeteners on Intestinal Nutrient-Sensing Receptors: Dr. Jekyll or Mr. Hyde?

The consumption of artificial and low-calorie sweeteners (ASs, LCSs) is an important component of the Western diet. ASs play a role in the pathogenesis of metabolic syndrome, dysbiosis, inflammatory bowel diseases (IBDs), and various inflammatory conditions. Intestinal nutrient-sensing receptors act as a crosstalk between dietary components, the gut microbiota, and the regulation of immune, endocrinological, and neurological responses. This narrative review aimed to summarize the possible effects of ASs and LCSs on intestinal nutrient-sensing receptors and their related functions. Based on the

Совпадение в полном тексте источника
… Maltitol, another low-calorie sugar alcohol that is derived from maltose via hydrogenation, could bind to the T1R2/T1R3 receptor complex and the T1R2 binding site [ 125 ]. Its sweetness and taste are comparable to sucrose. Maltitol has a slow absorption rate and is metabolized by colonic bacteria. …

The Link Between the Gut Microbiome and Bone Metastasis.

The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors an

Совпадение в полном тексте источника
… recruiting NCT06133530 | An interventional randomized study parallel assignment | Healthy state | To characterize bone formation/resorption markers, fecal calprotectin, inflammation markers in blood, fecal SCFAs, and gut microbiome | 26 participants | Prebiotic human milk oligosaccharide or placebo (maltose …

Сосуществование Лактиплантацилла и Виккерхамомиц в верхнем слое сахарного тростника стимулирует потенциальное подавление патогенов и аэробную стабильность за счет увеличения производства лактической кислоты и уксусной кислоты.

Чтобы определить сосуществующие бактерии и дрожжи в верхнем слое сахарного тростника, которые определяют качество ферментации и повышают безопасность корма, мы манипулировали эпифитической микробиотой сверху сахарного тростника путем селективного подавления дрожжей (АФ) или бактерий с лактической кислотой (АБ) перед повторной цензурой, используя в качестве контроля неочищенные (КК) и стерилизованные стерилизованные силизы (НА). Результаты показывают, что высокоурожайное производство лактической кислоты и уксусной кислоты (p) < 0.05), лучшая аэробная стабильность и высокая плотность Лактипланта

Совпадение в полном тексте источника
… The utilization of carbon sources such as glucose, lactose, maltose, mannitol, sucrose, arabinose, xylose, sorbitol, rhamnose, salicin, aescin, muscarin, raffinose, fructose, melibiose, cellobiose, starch, and galactose by the yeast and LAB strains was determined using microbial chemical reaction tubes …